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Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases

Hepatic macrophages play a central role in maintaining homeostasis in the liver, as well as in the initiation and progression of liver diseases. Hepatic macrophages are mainly derived from resident hepatic macrophages called Kupffer cells or circulating bone marrow-derived monocytes. Kupffer cells a...

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Autores principales: van der Heide, Daphne, Weiskirchen, Ralf, Bansal, Ruchi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901832/
https://www.ncbi.nlm.nih.gov/pubmed/31849997
http://dx.doi.org/10.3389/fimmu.2019.02852
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author van der Heide, Daphne
Weiskirchen, Ralf
Bansal, Ruchi
author_facet van der Heide, Daphne
Weiskirchen, Ralf
Bansal, Ruchi
author_sort van der Heide, Daphne
collection PubMed
description Hepatic macrophages play a central role in maintaining homeostasis in the liver, as well as in the initiation and progression of liver diseases. Hepatic macrophages are mainly derived from resident hepatic macrophages called Kupffer cells or circulating bone marrow-derived monocytes. Kupffer cells are self-renewing and typically non-migrating macrophages in the liver and are stationed in the liver sinusoids in contrast to macrophages originating from circulating monocytes. Kupffer cells regulate liver homeostasis by mediating immunity against non-pathogenic blood-borne molecules, while participating in coordinated immune responses leading to pathogen clearance, leukocyte recruitment and antigen presentation to lymphocytes present in the vasculature. Monocyte-derived macrophages infiltrate into the liver tissue when metabolic or toxic damage instigates and are likely dispensable for replenishing the macrophage population in homeostasis. In recent years, different populations of hepatic macrophages have been identified with distinct phenotypes with discrete functions, far beyond the central dogma of M1 and M2 macrophages. Hepatic macrophages play a central role in the pathogenesis of acute and chronic liver failure, liver fibrosis, non-alcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, and hepatocellular carcinoma, as well as in disease resolution. The understanding of the role of hepatic macrophages in liver diseases provides opportunities for the development of targeted therapeutics for respective malignancies. This review will summarize the current knowledge of the hepatic macrophages, their origin, functions, their critical role in maintaining homeostasis and in the progression or resolution of liver diseases. Furthermore, we will provide a comprehensive overview of the therapeutic targeting strategies against hepatic macrophages developed for the treatment of liver diseases.
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spelling pubmed-69018322019-12-17 Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases van der Heide, Daphne Weiskirchen, Ralf Bansal, Ruchi Front Immunol Immunology Hepatic macrophages play a central role in maintaining homeostasis in the liver, as well as in the initiation and progression of liver diseases. Hepatic macrophages are mainly derived from resident hepatic macrophages called Kupffer cells or circulating bone marrow-derived monocytes. Kupffer cells are self-renewing and typically non-migrating macrophages in the liver and are stationed in the liver sinusoids in contrast to macrophages originating from circulating monocytes. Kupffer cells regulate liver homeostasis by mediating immunity against non-pathogenic blood-borne molecules, while participating in coordinated immune responses leading to pathogen clearance, leukocyte recruitment and antigen presentation to lymphocytes present in the vasculature. Monocyte-derived macrophages infiltrate into the liver tissue when metabolic or toxic damage instigates and are likely dispensable for replenishing the macrophage population in homeostasis. In recent years, different populations of hepatic macrophages have been identified with distinct phenotypes with discrete functions, far beyond the central dogma of M1 and M2 macrophages. Hepatic macrophages play a central role in the pathogenesis of acute and chronic liver failure, liver fibrosis, non-alcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, and hepatocellular carcinoma, as well as in disease resolution. The understanding of the role of hepatic macrophages in liver diseases provides opportunities for the development of targeted therapeutics for respective malignancies. This review will summarize the current knowledge of the hepatic macrophages, their origin, functions, their critical role in maintaining homeostasis and in the progression or resolution of liver diseases. Furthermore, we will provide a comprehensive overview of the therapeutic targeting strategies against hepatic macrophages developed for the treatment of liver diseases. Frontiers Media S.A. 2019-12-03 /pmc/articles/PMC6901832/ /pubmed/31849997 http://dx.doi.org/10.3389/fimmu.2019.02852 Text en Copyright © 2019 van der Heide, Weiskirchen and Bansal. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
van der Heide, Daphne
Weiskirchen, Ralf
Bansal, Ruchi
Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases
title Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases
title_full Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases
title_fullStr Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases
title_full_unstemmed Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases
title_short Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases
title_sort therapeutic targeting of hepatic macrophages for the treatment of liver diseases
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901832/
https://www.ncbi.nlm.nih.gov/pubmed/31849997
http://dx.doi.org/10.3389/fimmu.2019.02852
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